Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXPASUM)

• DOT Name: Calcium homeostasis modulator protein 5 (CALHM5)
• Synonyms: Protein FAM26E
• Gene Name: CALHM5
• UniProt ID: CAHM5_HUMAN
• PDB ID: 7D60; 7D61; 7D65
• Pfam ID: PF14798
• Sequence:
  MDAFQGILKFFLNQKTVIGYSFMALLTVGSERLFSVVAFKCPCSTENMTYGLVFLFAPAW
  VLLILGFFLNNRSWRLFTGCCVNPRKIFPRGHSCRFFYVLGQITLSSLVAPVMWLSVALL
  NGTFYECAMSGTRSSGLLELICKGKPKECWEELHKVSCGKTSMLPTVNEELKLSLQAQSQ
  ILGWCLICSASFFSLLTTCYARCRSKVSYLQLSFWKTYAQKEKEQLENTFLDYANKLSER
  NLKCFFENKRPDPFPMPTFAAWEAASELHSFHQSQQHYSTLHRVVDNGLQLSPEDDETTM
  VLVGTAHNM
• Function: Pore-forming subunit of a voltage-gated ion channel.

Molecular Interaction Atlas (MIA) of This DOT

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Calcium homeostasis modulator protein 5 (CALHM5).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calcium homeostasis modulator protein 5 (CALHM5).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Calcium homeostasis modulator protein 5 (CALHM5).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Calcium homeostasis modulator protein 5 (CALHM5).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Calcium homeostasis modulator protein 5 (CALHM5).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Calcium homeostasis modulator protein 5 (CALHM5).	[8]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Calcium homeostasis modulator protein 5 (CALHM5).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Calcium homeostasis modulator protein 5 (CALHM5).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.